1-dimethylamino-4-chloro-4-phenylbutane salt of penicillin



Patented Oct. 6, 1953 1-DI1HETHYLAMINO-4-CHLORO-4-PHENYL- BUTANE SALT OF PENICILLIN Harley W. Rhodehamel, Jr.,

assignor to Eli Indianapolis, Ind.,

Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Drawing. Application February 13, 1952, Serial No. 271,437

2 Claims. (Cl. 260-2391) This invention relates to a novel penicillin salt and the preparation thereof.

I have discovered that l-dimethylaminolchloro-4-phenylbutane or its salts can be combined with penicillin or its salts by neutralization or metathetical reactions to form a sparingly soluble penicillin salt, thereby alfording a means of precipitating penicillin from solution, and of purifying penicillin. Moreover, the novel penicillin salt can be utilized therapeutically. A prolonged penicillin blood level can be secured upon administering the salt parenterally by methods known to the medical art.

The following examples illustrate the preparation of the novel salt of this invention:

Example 1 To a solution of 3 g. of penicillin (e. g. a commerclal mixture of the several penicillins) dissolved in 30 ml. of amyl acetate are added 3 g. of l dimethylamino 4 chloro 4 phenylbutane dissolved in 40 ml. of amyl acetate. The mixture is cooled and stirred occasionally whereupon the 1-dimethylamino-4-chloro-4-phenylbutane salt of penicillin precipitates. The salt is isolated as by decantation or filtration, and dried in vacuo.

The salt is represented by the following formula in which P represents penicillin:

/CH| ([IHCHaCHiCHPN 01 t CH:

Example 2 To an aqueous solution of 0.3 g. of the potassium salt of penicillin G in 1.8 ml. of Water is added a solution of 0.3 g. of l-dimethylamino-lchloro-4-phenylbutane hydrochloride in 5 ml. of water. The mixture is cooled and stirred occasionally whereupon the slightly soluble 1-dimethylamino-4-chl0ro-4-pheny1butane salt of penicillin G precipitates. The salt is separated, and dried in vacuo.

l dimethylamino 4 chloro 4 phenylbutane can be prepared as follows: Ethyl benzoylacetate is condensed with l-dimethylamino-2- chloroethane to form 1-benzoyl-3-dimethylamino propane, which is reduced to l-dimethylamino-4-phenylbutanol-4 with lithium aluminum hydride. The substituted butanol is treated with thionyl chloride to form l-dimethylamino-4-chloro-4-phenylbutane.

I claim:

1. The 1-dimethylamino-4-chloro-4-phenylbutane salt of penicillin represented by the following formula in which P represents penicillin:

2. The 1-dimethylamino-4-chloro-4-phenylbutane salt of penicillin G.

HARLEY W. RHODEHAIVIEL, J R.

References Cited in the file of this patent UNITED STATES PATENTS 

1. THE 1-DIMETHYLAMINO-4-CHLORO-4-PHENYLBUTANE SALT OF PENICILLIN REPRESENTED BY THE FOLLOWING FORMULA IN WHICH P REPRESENTS PENICILLIN: 